Gastrointestinal bleeding in adult patients with Meckel's diverticulum: The role of technetium 99m pertechnetate scan.

ABSTRACT: Obscure gastrointestinal (GI) bleeding is often challenging for the primary care physician, but with improved diagnostic testing the cause of this blood loss is determined in most patients. However, approximately 5% of the time no underlying cause is found. One common etiology in patients younger than 40 years of age is a Meckel's diverticulum. The technetium 99m pertechnetate scan is the standard test for making this diagnosis. However, the sensitivity of the scan is only 62% in the adult population. In this case report, a patient with profound, hemodynamically significant GI blood loss had multiple negative studies. Subsequently, an abnormal vascular Lesion was detected and during exploratory laparotomy, a Meckel's diverticulum was found and removed. Although the technetium pertechnetate scan is falsely negative in a number of cases, there are ways to increase its sensitivity and possibly avoid repeated testing.

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IN ABOUT 5% OF CASES of gastrointestinal (GI) hemorrhage, the source of bleeding is not identifiable, (1) and patients are often subjected to extensive and repetitive testing, including upper endoscopy, colonoscopy, and upper GI series (with contrast medium). (2, 3) When these initial studies are negative, further investigation includes scintigraphy with labeled red blood cells (RBCs), arteriography, technetium 99m pertechnetate (Meckel's) scan, enteroclysis, and/or small bowel enteroscopy. In patients more than 40 years old, vascular ectasias, Dieulafoy lesions, injury due to nonsteroidal anti-inflammatory drugs (NSAIDs), and cancer are the common causes. In patients younger than 40, however, small bowel cancer, Meckel's diverticulum, polyposis syndrome, and Crohn's disease are often found. (1)

Meckel's diverticulum, a vestige of the omphalomesenteric duct, is the most common congenital GI anomaly, causing nearly 50% of all cases of lower GI bleeding in patients less than 3 years of age. (4) This anomaly represents a true diverticulum and may contain heterotopic gastric tissue. (5) The presence of gastric mucosa in the diverticulum increases the risk of GI hemorrhage. (6) The German anatomist Johann Friedrich Meckel meticulously described this entity in the 19th century. (7) The technetium 99m pertechnetate scan is the test of choice for detecting Meckel's diverticulum, with a reported sensitivity of 85% to 90% in the pediatric population. (8) In adults, however, the sensitivity falls to only 62%. (4) False-negative studies may be due to improper technique, pooling of the radioactive material in the stomach or bladder, or a paucity of ectopic gastric mucosa. (4) Several modifications that may be used to improve this diagnostic yield are premedication with histamine receptor antagonist with or witho ut pentagastrin, bladder lavage, and nasogastric suctioning. (9-13) Recently, a modification of the standard Meckel's scan using single photon emission computed tomography (SPECT) has been shown to detect heterotopic gastric mucosa. (14) However, the sensitivity and specificity of this technique in the diagnosis of Meckel's diverticulum has not been reported. This case report of GI blood loss in a patient who had a false-negative Meckel's scan illustrates the need to pursue modifications in technetium pertechnetate scans to minimize false-negative results.

CASE REPORT

A 24-year-old man with a 5-year history of occult GI blood loss was seen in the emergency department (ED) for evaluation of bright red blood per rectum, melena, dizziness, and fatigue. In the ED, he was found to be orthostatic with melenic stools. The hematocrit value was 28%. Nasogastric lavage yielded clear fluid. While in the ED, the patient had an observed bowel movement of dark red stool with clots. He was given transfusions of normal saline and blood and was admitted for further evaluation. He had been assessed at another hospital 5 years earlier with numerous upper endoscopies, colonoscopies, small bowel follow-through, scintigraphy with labeled RBCs, a Meckel's scan, small bowel enteroscopy to the proximal jejunum, and a study via sonde enteroscope passed to the mid-ileum, all of which yielded negative results. (The sonde method of endoscopy involves passage of a long enteroscope through the nares to the distal duodenum. The enteroscope has a balloon at its tip. With the balloon inflated, normal bowel peristalsis moves the enteroscope through the small intestine into the distal ileum. After 6 to 8 hours, the endoscopist with direct visualization of the small bowel removes the endoscope.)

The patient had no history of alcohol, NSAID use, or tobacco use, and his only daily medication was a proton pump inhibitor. He had no known coagulopathy, and evaluation included a scan with labeled RBCs, an upper endoscopy to the mid-duodenum, a colonoscopy to the terminal ileum, a small bowel enteroscopy to the mid/distal jejunum, and an enteroclysis; all findings were normal. The Meckel's scan (Fig 1) was obtained from the outside hospital and was reviewed, and the scan was not repeated. The patient then had elective superior mesenteric, celiac, and inferior mesenteric arteriography with heparin/urokinase/tolazoline HCl (Priscoline) challenge (Fig 2). An abnormal ectatic vessel seen in the region of the distal ileum was thought to be a vascular anomaly. No active bleeding was induced by the heparin and tolazoline challenge. The patient was readmitted for elective diagnostic laparotomy. At operation, a Meckel's diverticulum was found and resected. Pathology confirmed the diagnosis of Meckel's diverticulum w ith copious ectopic gastric mucosa and a 1 to 2 cm ulcer. The patient had no postoperative complications and was discharged. After the resection, with more than 3 years of follow-up, the patient had no more episodes of GI bleeding.

DISCUSSION

This case shows that occult GI bleeding may often present a diagnostic challenge to the physician. Many patients have extensive studies without a definitive diagnosis. Although lesions in the small bowel may cause many episodes of occult GI bleeding, such studies as small bowel enteroscopy and enteroclysis may not be first line in diagnostic testing. In 1994, Chong et al (15) reviewed push enteroscopy in 55 patients with occult GI bleeding. Although a source of bleeding was found in 64% of the patients, 60% had lesions proximal to the ligament of Treitz that should have been diagnosed by previous esophagogastroduodenoscopy. (15) Additionally, Chak et al (16) reviewed push enteroscopy in a group of 164 patients with occult GI bleeding. Of the 56% of these patients found to have a diagnosis, 40% of them had proximal lesions that were presumably overlooked by previous endoscopy. Although not the case in our patient, it is likely that repeated endoscopy before other interventions such as the enteroscopy, enterocl ysis, scanning with labeled RBCs, or the Meckel's scan will provide a diagnosis. (17)

When results of upper and lower endoscopies are negative, the next appropriate area to examine is the small bowel. Indeed, small bowel lesions are responsible for chronic GI blood loss in a small but significant group of patients. In a young patient, such as the one presented here, lesions likely to be found include small bowel tumors, Crohn's disease, vascular ectasias, and/or Meckel's diverticulum. (1) Although a Meckel's diverticulum is most often seen in patients less than 2 years of age, a case has been reported in a patient 93 years old. (18) The incidence of Meckel's diverticulum in the general population is 2%, and ectopic gastric mucosa is found in only 60% of these diverticula. (4) However, of the diverticula manifested by occult GI bleeding, nearly 90% possess gastric mucosa. (4) The presence of the gastric mucosa is the likely reason for GI bleeding. This acidic environment may lead to ulcer formation within the diverticula.

Harper et al (19) initially introduced the technetium 99m pertechnetate scan in 1962 as a method of diagnosing Meckel's diverticulum because of the tracer's propensity to concentrate in gastric mucosa. In 1970, Jewett et al (20) were the first to clinically apply this method. Since that time, the Meckel's scan has gained popularity as the diagnostic test of choice for patients with suspected Meckel's diverticulum. Sfakianakis and Conway (8) reviewed 954 Meckel's scans in 917 patients from 46 reports and calculated that the scan had a sensitivity of 85%, a specificity of 95%, and an overall accuracy of 90%. However, nearly 90% of the patients in their study were pediatric patients. In a review of the literature reporting Meckel's diverticulum in the adult population (16 years or older), Schwartz and Lewis (4) found limited data for this age group. Of the 184 patients reviewed, only 37 had complete records. In this group, the scan was found to have a sensitivity of only 62.5% and a positive predictive value of only 60.0%, much lower diagnostic values than for the pediatric population. (4) Although the numbers were small, the results tend to show that the Meckel's scan alone may be less useful in the older population.

One cause of a false-negative Meckel's scan is insufficient or absent gastric mucosa in the diverticulum. This situation occurs more often in the adult population, since diverticula with more abundant gastric mucosa would likely cause bleeding earlier in life. One method to counterbalance this situation is to increase the uptake and/or activity of the gastric mucosa cells present. Pentagastrin is thought to increase acid production from the gastric parietal cells and thus concomitantly to increase the activity of the mucus-producing cells. (11) In 1978, Treves et al (10) showed that pentagastrin increased the uptake of technetium pertechnetate in gastric mucosa. In a case report, a patient with previously negative results on Meckel's scan was given subcutaneous pentagastrin, and findings on a subsequent test were positive. The diagnosis of Meckel's diverticulum was then later confirmed by laparotomy. (10) In addition to pentagastrin, histamine receptor antagonists are postulated to work by blocking secretions from the gastric mucosal cells, thus leading to increased accumulations of the radionuclide tracer. (11) This effect was first shown by Petrokubi et al (9) in 1978. Since that time, numerous case reports have shown that the use of [H.sub.2] receptor antagonists increases the uptake of pertechnetate in Meckel's diverticula that contain ectopic gastric mucosa. (9,11,12) There are also some reports on the use of pentagastrin in combination with [H.sub.2] receptor antagonists. Heyman (12) described a patient who was given pentagastrin and initially had a negative scan, but a later scan when both pentagastrin and ranitidine hydrochloride were administered showed positive findings that were confirmed by laparotomy. No randomized trials have been done to determine the sensitivity of the Meckel's scan with the use of pentagastrin or [H.sub.2] receptor antagonists or both. However, from reviewing the numerous case reports, it is reasonable to deduce that the use of these medications as a modification to the technetiu m pertechnetate scan may increase the rate of detection of Meckel's gastric mucosa in the older patient population.

Another modification of the Meckel's scan involves a saline lavage of the bladder during the procedure. (4) Although few case reports indicate tracer pooling in the bladder as a cause of false-negative scans, there have been numerous cases in which the accumulation of the tracer in urine have caused false-positive scans. (13,21) For example, Datz and Taylor (21) described a patient who initially had a focus of activity in the region of the bladder that later disappeared with saline irrigation, indicating a bladder diverticulum. Again, it is reasonable to assume that bladder lavage, by removing tracer that may obscure the terminal ileum, would not only decrease the chance of false-positive scans, but also possibly false-negative results. In our case study, the use of this technique may have led to the correct diagnosis. The diverticulum was clearly obscured by the tracer concentration in the bladder, leading to a negative study.

The collection of radioactive tracer pooled in the gut has also been reported in the literature as a cause of false-positive scans. Singh et al (13) reviewed two case reports in which patients with positive Meckel scans had these results reversed after receiving nasogastric suction, indicating radioactive tracer pooling as the cause of the false-positive study. Although no cases in the literature have reported pooling in the gut as a cause of false-negative scans, it may be reasonable to assume that pooling of the tracer in the stomach may at times obscure positive test results.

CONCLUSION

The technetium 99m pertechnetate scan may be a useful tool in the workup of a patient with occult GI bleeding. However, in our patient, the false-negative scan led to unnecessary further testing. Because of the fall in sensitivity of the Meckel's scan in the adult population, premedication with a histamine receptor antagonist with or without pentagastrin, saline lavage of the bladder, and nasogastric suctioning may improve the diagnostic yield and prevent unneeded diagnostic procedures.

References

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(3.) Rockey DC: Occult gastrointestinal bleeding. N Engl J Med 1999; 341:38-46

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(9.) Petrokubi RJ, Baum S, Rohrer GV: Cimetidine administration resulting in improved pertechnetate imaging of Meckel's diverticulum. Clin Nucl Med 1978; 3:385-388

(10.) Treves S, Grand RJ, Eraklis AJ: Pentagastrin stimulation of technetium-99m uptake by ectopic gastric muscosa in a Meckel's diverticulum. Radiology 1978; 128:711-712

(11.) Diamond RH, Rothstein RD, Alavi A: The role of cimetidine-enhanced technetium-99m-pertechnetate imaging for visualizing Meckel's diverticulum. J Nucl Med 1991; 32:1422-1424

(12.) Heyman S: Meckel's diverticulum: possible detection by combining pentagastrin with histamine [H.sub.2] receptor blocker. J Nucl Med 1994; 35:1656-1658

(13.) Singh PR, Russell CD, Dubovsky EV, et al: Technique of scanning for Meckel's diverticulum. Clin Nucl Med 1978; 3:188-192

(14.) Connolly LP, Treves ST, Bozorgi F, et al: Meckel's diverticulum: demonstration of heterotopic gastric mucosa with technetium-99m-pertechnetate SPECT. J Nucl Med 1998; 39:1458-1460

(15.) Chong J, Tagle M, Barkin JS, et al: Small bowel push-type fiberoptic enteroscopy for patients with occult gastrointestinal bleeding or suspected small bowel pathology. Am J Gastroenterol 1994; 89:2143-2146

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RELATED ARTICLE: KEY POINTS

* We review the diagnostic approach to recurrent gastrointestinal bleeding of unknown etiology and the common etiologies for this problem in adults.

* We show the sensitivity of the Meckel's (technetium 99m pertechnetate) scan in paients with gastrointestinal bleeding.

* We discuss mechanisms to increase the sensitivity of the Meckel's scan in adult patients and possibly avoid unnecessary diagnostic testing.

From the Departments of Surgery, Medicine, and Radiology, Duke, University Medical Center and Durham VA Medical Center, Durham, NC.

Reprint requests to Michael A. Shetzline, MD, Duke University Medical Center, Division of Gastroenterology, Box 3083, Durham, NC 27710.